The overall objective of the presently proposed research is two-fold: A) to establish at the ultrastructural level, the characteristics of the surface membrane of sporozoites of mammalian malaria, and B) to investigate the mode of interaction of these parasites with immune serum, and its effects on parasite-host cell interaction, particularly the uptake of sporozoites by macrophages, and their penetration into liver cells. It is planned to approach this through investigation of the morphological characteristics of the surface membranes of sporozoites by means of negative staining and scanning electron microscopy; through defining the ultrastructural changes resulting from the interaction of antisporozoite antisera and this parasite stage, in an attempt to clarify the mechanism of antibody-induced "sporozoite neutralization"; through determining the presence and distribution of antigen(s) on the surface membrane of salivary gland sporozoites; through defining some of the cytochemical properties of the surface membrane of sporozoites; through investigating the in vitro interaction of macrophages obtained from normal, immune, and non-specifically stimulated animals with sporozoites pre-incubated in either normal or immune sera; through investigating, in vitro, the invasion of liver cells by sporozoites using hepatocytic lines maintained in culture. These investigations should hopefully provide an answer to a number of basic questions on malaria host-parasite interaction. Some of these questions, particularly with regard to antigens of the surface membrane, the mechanism(s) of sporozoite-antibody interaction and their possible effects on host cell invasion by the parasite, are, we believe, of fundamental importance with regard to the elucidation of mechanism(s) of protective immunity and the development of a future malarial vaccine. BIBLIOGRAPHIC REFERENCES: Cochrane, A.H., Aikawa, M., Jeng, M. and Nussenzweig, R. S. 1976. Antibody-induced ultrastructural changes of malarial sporozoites. J. Immunol. 116: 859-867. Nussenzweig, R.S., Cochrane, A.J., and Lustig, H.J. Immunological response to murine malaria. In: Malaria Parasites of Rodents, eds. W. Peters and R. Killick-Kendrick. Academic Press, 1977.